The purpose of this project is to delineate the mechanisms involved in regulating the humoral and cellular responses in patients with filariasis and other disease states and to determine those antigens responsible for inducing these responses. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by demonstrating this anergy at the level of antibody (B cell) and lymphokine (T cell) responsiveness. Further, similar T cell anergy has been found among patients with active onchocerciasis. The influence of genetic factors and antigen composition on this anergy has begun using molecular biologi-cal tools and defined antigens. In vitro models of parasite-antigen driven antibody production as well as parasite-specific and HTLV-I transformed T cell clones have been developed to understand in more detail those mechanisms regulating antibody production (particularly IgG and IgE) in filarial and non-filarial diseases. Qualitative analysis of filaria-specific IgE and IgG in loiasis, lymphatic filariasis, and onchocerciasis have indicated patterns of antigen recognition which differ among groups of patients with different clinical manifestations of filariasis. Using these techniques, antigens recognized exclusively by patients with loiasis or onchocerciasis have been identified. Filarial species- specific antigens recognized by human monoclonal antibodies derived from EBV-transformed patient B cells have also been identified and characterized. Further, FPLC fractionation and qualitative analysis of the antigenic components of filarial parasites has identified two sets of proteins which appear to regulate the immune response at both the cellular and humoral level.